Introduction: Frailty, a syndrome of physiologic vulnerability, increases cardiovascular disease (CVD) risk via overlapping mechanisms such as inflammation, insulin resistance, and cellular senescence. However, the association of frailty with incident heart failure (HF) has not been well characterized. We calculated three distinct frailty scores and examined their association with HF in the Million Veteran Program (MVP). Methods: Participants comprised U.S. Veterans aged 50 years or older at baseline (2011-2018) enrolled in the prospective MVP study who were free of HF. We calculated frailty using three validated approaches: primarily the 36-item MVP-frailty index (FI) based on questionnaire data, 31-item Veterans Administration-FI (VA-FI) EHR-based index, and the 3-item Study of Osteoporotic Fractures (SOF) physical frailty score. Incident HF was ascertained via ICD-9 and ICD-10 codes. Multivariable-adjusted Cox proportional hazards models were constructed to assess the association between frailty status via each index and incident HF. Results: Among 190,688 Veterans (aged 69 ±9 years, 94% male), using the MVP-FI frailty screening tool, 29% were robust, 42% were pre-frail, and 29% were frail. Frailty prevalence increased by age, from 27% among 50-59-year-olds to 42% among those 90 years or older. Over a mean follow-up of 6±2 years, 15,816 (8.3%) Veterans developed incident HF. Pre-frail and frail compared to robust Veterans had nearly a 1.5-fold and 3-fold hazard of HF, respectively. The VA-FI and SOF indices yielded concordant findings (Table). Conclusion Among US Veterans aged 50 years or older, frailty was associated with incident HF. A graded increase in the hazard of HF occurred with increasing level of frailty, irrespective of frailty tool used. The present analysis lays the groundwork for future studies needed to further define the role of frailty in the pathogenesis of HF and inform clinical interventions for prevention of frailty and downstream HF.